The objective of the research proposed in this Project is to evaluate a potential nutritional alternative to CEE replacement therapy that would provide a beneficial effect on postmenopausal CHD and osteoporosis but would be free of adverse effects on the breast and uterus. We have chosen to focus on the phytoestrogens of soybeans (genistein and daidzein) because: Asian women who consume diets relatively high in the soybean estrogens (SBE) have a low occurrence of postmenopausal CHD. An extensive literature exists suggesting that genistein has important inhibitory effects at several levels of atherogenesis. Data obtained in our laboratory indicate favorable effects of SBE on plasma lipid and lipoprotein profiles. The literature to date suggests a protective effect of SBE against the development of breast cancer and a lack of effect on the endometrium. Epidemiologic and experimental evidence suggests that phytoestrogens prevent bone loss postmenopausally. Nutritional supplements rich in these phytoestrogens are available. One hundred eighty-nine surgically postmenopausal monkeys were randomized into three groups (all fed a moderately atherogenic diet): one group fed a soy isolate with only trace amounts of genistein and daidzein as the source of dietary protein (Group 1); one fed the same diet with conjugated equine estrogens added at a dose equivalent for a woman of 0.625 mg/day (Group 2); and one fed a soy isolate with the naturally occurring amounts of genistein and daidzein (1.7 mg/g) (Group 3). The aims of the research are to quantify the relative effectiveness of CEE and SBE in inhibiting the progression of postmenopausal coronary artery atherosclerosis, the effects of treatment with CEE and SBE on mammary gland and endometrial hyperplasia, the relative effectiveness of CEE and SBE in inhibiting postmenopausal bone loss, and whether CEE and SBE treatment results in a disassociation of the relationship between cardiac hyperactivity and exacerbated coronary artery atherosclerosis we have observed for estradiol.